Cold sterilant solution

ABSTRACT

A sterilant-disinfectant solution which may be used in the cleaning of metallic objects, particularly medical instruments. Medical instruments, which may include brass, copper, aluminium, stainless steel, carbon steel or plastic parts are sterilized or disinfected in an anti-microbial solution. The solution includes a triazole or other component for inhibiting the corrosion of copper and brass. Phosphates or other buffering agents adjust the solution pH in order to prevent the corrosion of steel. Molybdates or analogous compounds may be used to buffer the pH and have been found to inhibit the corrosion of aluminium by oxidizing agents. A sequestering agent is preferably provided for inhibiting hard water precipitation.

This is a Continuation of application Ser. No. 08/333,431, filed Nov. 2,1994.

The present invention relates to a sterilant-disinfectant solution whichmay be used in the cleaning of metallic objects, particularly medicalinstruments. Medical instruments, which may include brass, copper,aluminium, stainless steel, carbon steel or plastic parts are sterilizedor disinfected in an anti-microbial solution. The solution includes atriazole or other component for inhibiting the corrosion of copper andbrass. Phosphates or other buffering agents adjust the solution pH inorder to prevent the corrosion of steel. Molybdates or analogouscompounds may be used to buffer the pH and have been found to inhibitthe corrosion of aluminium by oxidizing agents. A sequestering agent ispreferably provided for inhibiting hard water precipitation.

BACKGROUND OF THE INVENTION

In medical diagnosis and therapy, open surgical operations are beingreplaced to an increasing extent by the use of endoscopes. However,flexible glass fibre endoscopes become massively infected withmicroorganisms which are present in body cavities, on the mucousmembrane, and in the blood. Accordingly, used endoscopes have to bethoroughly cleaned and disinfected after each use.

Glass fibre endoscopes are extremely complicated precision instrumentswhich have moving parts and which are made from a number of materials.They are extremely difficult to clean and disinfect for a number ofreasons. Not only the outer surfaces of the instrument, but also thenarrow bores present in the interior have to be cleaned and disinfected.In view of the sensitivity of the materials involved, cleaning anddisinfection have to be performed in such a way that no residues of thepreparation used remain on the treated surfaces of the instrument. Theextremely effective process of thermal sterilization normally used formedical instruments cannot be applied to endoscopes because endoscopesare made partly of temperature-sensitive materials. Another factor to betaken into consideration is that many of the metal parts present aresusceptible to corrosion. Finally, endoscopes should be able to becleaned and disinfected in a short time so that they are always ready ingood time for the treatment of the next patient.

While the process of the invention has particular application toendoscopes, the process can be used to clean and sterilize othersurgical, medical, or dental devices and equipment, or in fact anyequipment or devices having hard surfaces for any use where cleaning anddisinfecting such hard surfaces is desired, particularly equipment anddevices that cannot tolerate high temperature cleaning andsterilization.

CHLORINE DIOXIDE AS STERILANT

Chlorine dioxide is an extremely effective sterilant and bactericide,equal or superior to chlorine on a mass dosage basis. Its efficacy hasbeen well documented in the laboratory, in pilot studies and infull-scale studies. Unlike chlorine, chlorine dioxide does not hydrolysein water. Therefore, its germicidal activity is relatively constant overa broad pH range.

At pH 6.5, doses of 0.25 mg/l of chlorine dioxide and chlorine producecomparable one minute kill rates for the bacterium Escherichia coli. AtpH 8.5, chlorine dioxide maintains the same kill rate, but chlorinerequires five times as long. Thus, chlorine dioxide should be consideredas a primary sterilant in high pH, lime-softened waters.

Chlorine dioxide has also been shown to be effective in killing otherinfectious bacteria such as Staphylococcus aureus and Salmonella.Chlorine dioxide is as effective as chlorine in destroying coliformpopulations and is superior to chlorine in the treatment of commonlyfound viruses. In a test, Poliovirus 1 and a native coliphage weresubjected to these two disinfectants. A 2 mg/l dose of chlorine dioxideproduced a much lower survival rate than did a 10 mg/l dose of chlorine.

A sterilant must provide specified levels of microorganism kills orinactivations as measured by reductions of coliforms, heterotrophicplate count organisms and Legionella bacteria. Disinfection is currentlydefined by the Environmental Protection Agency to mean 99.9 per centreduction in the Giardia lamblia cyst levels and 99.99 per centreduction in enteric virus concentrations. Disinfection is expressed asa CT. value (i.e. a function of Concentration×Contact Time). At the CTvalues necessary for chlorine dioxide to inactivate 99.9 per cent ofGiardia lamblia cysts, the simultaneous inactivation of 99.99 per centof enteric viruses is also assured.

ACTIVATING ACID

Although chloride dioxide has been found to be an excellent sterilant,it is difficult to use in direct form. In gaseous state, chloridedioxide is explosive and poisonous. Accordingly, sodium chlorite is usedas a chloride dioxide-liberating material. Chloride dioxide may beliberated from the sodium chlorite (or any other suitable liberatingmaterial) by the addition of a suitable activating system, most usuallyan acid. Various inorganic and organic acids have been tested asactivating systems. A description of the various acid systems which maybe used is given in EP-A-0176558 (Alcide Corporation). Preferred acidsare lactic acid, phosphoric acid, acetic acid, sorbic acid, ascorbicacid, phosphoric acid and hydrochloric acid. It is preferred that theacid should be present in an amount from 0.01 to 10% based on the totalweight of the composition. Citric acid is a preferred acid for use inactivation. Combinations of suitable acids may be used, e.g. acombination of sorbic, boric and citric acid. Such a combination ispreferred as the sorbic and boric acid act not only as activators butalso as bactericides in their own right. A higher "kill" is found thanif using citric acid alone or in combination with, for example, lacticacid.

CORROSION INHIBITION

Many liquid sterilization systems are highly corrosive to metal parts,particularly brass, copper, and aluminium. With long immersion times,even carbon steel and stainless steel could be pitted and sharp cuttingedges dulled.

The use of a simple sodium chlorite/acid activator system as asterilizer of various instruments leads to corrosion of metal parts, dueto the aqueous basis of the system. The corrosion means that expensiveinstruments have a shortened lifetime.

A number of corrosion inhibitors are available and are well-known.However, if an oxidizing agent, for example chlorine dioxide, is to beused as the sterilizing agent, various problems must be overcome inselecting suitable inhibitors. The main problem is that the inhibitorsmust be effective in powerful oxidizing solutions where chloride ionsare present. Furthermore, the inhibitors must be stable under long-termstorage in acidic conditions, and must not react together to formdeposits or harmful reaction products. The inhibitors should not presenta health hazard, either when left in trace quantities on the sterilizedinstruments or prior to use.

The cleaning environment also produces special problems. The oxygenliberating agent is acidic. Because a number of different metals may bein the sterilizing tank at the same time, galvanic corrosion may beinitiated. There is a need to overcome this.

In accordance with the present invention, a new and improvedanti-microbial composition is provided which overcomes the overproblems. An anti-microbial solution is provided which comprises anoxidizing anti-microbial agent, a copper and brass corrosion inhibitorand buffering agent, a wetting agent and sequestering agent.

The oxidizing anti-microbial agent can be selected from the classconsisting of ozone, peracetic acid, organic peroxides, hydrogenperoxides, inorganic peroxides, and other oxygen releasing compounds,chlorine, chlorine dioxide, active chlorine releasing compounds such aschloramines, hypochlorites and phenol.

The copper and brass corrosion inhibitor is selected from the classconsisting essentially of triazoles, azoles, benzoates, and fivemembered ring compounds. Triazoles, particularly benzotriazole andtolytriazole are preferred as being stable in the presence of strongoxidizing compounds. Benzotriazole is most preferred as it also helps toprevent galvanic corrosion in mixed metal systems. Mercaptobenzathiozalmight also be utilized but may be destabilized by strong oxidizers. Theymight be present at 0.01 to 2.0 wt. % of the sterilizer system.

The aluminium and steel corrosion inhibitor and the buffering agent maybe selected from the class consisting essentially of chromates,dichromates, borates, nitrates, phosphates, molybdates, vanadates andtungsdates. More specifically to the preferred embodiment, phosphatesare preferred of inhibiting steel corrosion and buffering the solution.Molybdates are preferred for inhibiting aluminium corrosion andnitrates, particularly sodium nitrate, for inhibiting steel and ferriccorrosion.

The anti-corrosive buffering compounds may include a mixture ofphosphate in sufficient volume to produce a final concentration of 1.25weight per Volume and molybdates in an appropriate amount to produce afinal solution of 0.11% weight per volume. Phosphates may also beeffective in the range of 0.2% to 12% and the molybdates may beeffective from 0.1% to 10%. Optionally, chromates, dichromates,tungstates, vanadates, other borates, and combinations thereof may besubstituted in appropriate concentrations to inhibit steel corrosionsand aluminium corrosion.

Amines are often used as corrosion inhibitors. However, aminederivatives were rejected because of unpredictable film formingproperties.

In hard water, calcium and magnesium salts can precipitate and coat theinstruments being sterilized. A sequestering agent appropriate toprevent precipitation, such as sodium hexametaphosphate, may beprovided; if deionized or soft water is utilized the sequestering agentmay be eliminated. However, to ensure universal applicability with anywater that might be utilized, the presence of a sequestering agent ispreferred. It has been found that sodium citrate and trisodium phosphatealso act as sequestering agents.

A wetting agent present from 0.1 to 100 wt. %, preferably 1.0 to 5.0 wt.%, improves the wetting of the surface of the instrument by theanti-microbial agent. The wetting agent has also been found to increasepenetration of the anti-microbial improving anti-microbial efficacywhile reducing corrosion. Defoamers and preservatives may also beincluded, at levels of 0.01 to 1 wt. %.

EXAMPLE 1 Effect of Activating Acid

The possible contribution of acid used to activate (base) sodiumchlorite (convert the stabilised chlorine dioxide into free chlorinedioxide) towards the biocidal activity of chlorine dioxide has beeninvestigated. Listeria monocytogenes ATCC 15313 was used as the testorganism to eliminate acid sensitivity (characteristic of some gramnegative cubacteria such as Pseudomonas aruginos) as an experimentvariable. L. monocytogenes was grown on a modified synthetic broth asdescribed in A.O.A.C. Methods amended by the addition of Soytone, 3g/liter, to support growth.

Cultures were incubated for 24 hours at 37° C.

The acids tested are tabulated below. HCl was selected as a stronginorganic acid. Phosphoric acid, H₃ PO₄ was selected as anotherinorganic acid and was selected because of its common use in dairyprocessing plants. Lactic acid was chosen because claims have been madethat lactic acid contributes to the anti-microbial activity of theproduct. Citric acid is another organic acid and is the acid used toactivate the stabilised chlorine dioxide for its use as agermicide/disinfectant. Ascorbic acid is a third organic acid which isalso a mild reducing agent; it was tested to determine if thecombination of a reducing agent with the oxidising chlorine dioxidewould still be biocidal or be more active than chlorine dioxide alone. Acombination of sorbic acid, boric acid and citric acid was also usedbecause of their antimicrobial activity, and was found to beparticularly effective.

Sodium chlorite was activated as follows: 2× of the normal level ofactivating acid was added to a 100 ml graduated cylinder. 5.0 ml sodiumchlorite solution was added. After 2 minutes the solution was diluted to100 ml with deionized water, yielding a 1,000 ppm (calculated) stock ofchlorine dioxide.

1.0 ml of culture of L. monocytogenes was added to synthetic hard water,100 ppm hardness, and chlorine dioxide was added at 25 and 50 ppm(calculated) to initiate the test. The test volume was 50 ml.

Time points were taken at 30 and 60 seconds by adding 1.0 ml of a testto 4.0 ml of sodium thiosulfate (2,000 ppm). This was serially dilutedand plated for enumeration in the original growth medium containing 10g/liter purified agar. Viable cell counts were determined after 48 hoursof incubation at 37° C.

Results

After activation, the levels of chlorine dioxide were compared by eyeand were: HCl>H₃ PO₄ >lactic acid=citric acid>ascorbic acid. The amountof chlorine dioxide formed was a function of the pk_(a) of theactivating acid and not the level of acid (in this experiment); an acidwith a lower pk_(a) produced more chlorine dioxide than an acid with ahigher pk_(a).

The antimicrobial activity was a function of the apparent level ofchlorine dioxide formed upon activation. Thus, an activating acid with alower pk_(a), which produced more ClO₂, produced a solution with agreater level of biocidal activity. A combination of acid activatorsshowed a synergistic effect, giving results as good as those produced byan activator with a lower pk_(a).

    ______________________________________                                        EFFECT OF ACTIVATING                                                          ACID ON SODIUM CHLORITE SOLUTION                                                              Viable Cell Count/ml                                          Acid        ppm       30 seconds                                                                              60 seconds                                    ______________________________________                                        HCl         25         3 × 10.sup.3                                                                     <2 × 10.sup.6                                                  5 × 10.sup.6                                                                     <2 × 10.sup.6                           HCl         50        <2 × 10.sup.6                                                                     <2 × 10.sup.6                                                 <2 × 10.sup.6                                                                     <2 × 10.sup.6                           H.sub.3 PO.sub.4                                                                          25        <2 × 10.sup.6                                                                     <2 × 10.sup.6                                                  2 × 10.sup.2                                                                      1 × 10.sup.1                           H.sub.3 PO.sub.4                                                                          50        <2 × 10.sup.6                                                                     <2 × 10.sup.6                                                 <2 × 10.sup.6                                                                     <2 × 10.sup.6                           Citric acid 25         5 × 10.sup.4                                                                      3 × 10.sup.3                                                  4 × 10.sup.2                                                                      4 × 10.sup.1                           Citric acid 50         3 × 10.sup.1                                                                      8 × 10.sup.6                                                  6 × 10.sup.2                                                                      4 × 10.sup.1                           Ascorbic acid                                                                             25         1 × 10.sup.7                                                                      1 × 10.sup.7                                                  4 × 10.sup.7                                                                      1 × 10.sup.7                           Ascorbic acid                                                                             50         3 × 10.sup.6                                                                      4 × 10.sup.6                                                  4 × 10.sup.6                                                                      4 × 10.sup.6                           Sorbic acid                       <2 × 10.sup.6                         Citric acid     50        <2 × 10.sup.6                                 Boric acid                <2 × 10.sup.6                                                                   <2 × 10.sup.6                         ______________________________________                                         Control: 6 × 10.sup.6 /ml Listeria monocytogenes ATCC 15313        

EXAMPLE 2 Corrosion Inhibition

Endoscope Materials

Metallic components from the Olympus® endoscopes were used as testpieces. They comprised austenitic stainless steel (BS303,316), glass(Q2121) aluminium and two silicon-bearing aluminium alloys, A12011T3 andA16262T9 respectively. All of these materials are likely to besusceptible to attack by acid solutions of chloride ions, although thereis little risk from ClO₂ itself.

Corrosion Test Procedure

The test involves imposing on the test specimen a steadily increasingaggressive potential and observing the resulting anodic current. (Thisis a potentiodynamic procedure.) Until active corrosion (pitting)occurs, low anodic currents allow some comparison of the respectivestabilities of metallic components and the likelihood of galvaniceffects. The potential corresponding to the establishment of pitting isa measure of the effectiveness of intrinsic passivity or of inhibition.

In practice, a single open cell is used which contains the test piece,suitably mounted as an electrode, a calomel reference electrode and aniridium counter electrode. The potential between the test electrode andthe reference is monitored and controlled by a Solartron InstrumentsElectrochemical Interface (Type 1286) which supplies the measured andrecorded corrosion current via the iridium counter counter electrode.

Test electrodes are immersed in the electrolyte until the open circuitpotential stabilizes. The potential is then swept anodically untilpassivation for inhibition breaks down. It is an important feature ofthe experiment that the applied potential should change slowly(typically 0.5 mV sec⁻¹) to allow the surface phases to respond.

The cell was held at 20° C.

The electrolytes correspond to working biocidal solutions with orwithout inhibitor.

Results

Uninhibited Solution

Uninhibited electrolyte was harmless to the stainless steels but wasaggressive towards brass and both pure aluminium and its two alloys. Inpractical use there would be a risk of contamination of stainless steelcomponents with corrosion products (notably copper) from brass. Thiscould lead to harmful galvanic effects. Aluminium and its two alloys didnot withstand the solution without inhibitors.

It is unlikely that the test pieces would experience conditions in thefield as aggressive as those which have produced failures in thelaboratory, unless severely contaminated or held for unreasonably longperiods in used biocide.

Inhibited Solution

Very good inhibition was expected and found on the stainless steels.There was a notable improvement in performance of brass in theseelectrolytes and this promises well for the behaviour of multi-metalarticles. Excellent inhibition of aluminium was obtained.

The duration of the corrosion tests was longer than the recommendedsterilizing time; immersions of 2 hours at the open circuit potentialswere harmless to the test pieces. Potentials of metals (and potentialdifferences) between metal components are unlikely to produce acorrosive effect greater than that corresponding to -0.2V in the presentexperiments, so that a large "reserve" of corrosion resistance isprovided by the inhibitor formulation.

Conclusion

It was concluded that the solution with inhibitor provided more thanadequate protection of the metal parts from the biocide even when usedfor extended immersion periods, four times longer than recommended.

EXAMPLE 3

The following two-part sterilizing system was prepared:

    ______________________________________                                                             Wt %.                                                    ______________________________________                                        A        Sodium Chlorite Solution                                                      25% Sodium Chlorite Solution                                                                    9.2                                                         Demineralized water                                                                             →100                                        B        Acid Activator                                                                Citric Acid       6.0                                                         Sorbic Acid       1.0                                                         Boric Acid        1.0                                                         Sodium Citrate    2.5                                                         Trisodium Phosphate                                                                             2.5                                                         Benzotriazole     0.1                                                         Sodium Molybdate  0.5                                                         Sodium Nitrate    2.0                                                         Defoamer, Wetting Agent,                                                                        1.5                                                         Preservatives                                                                 Demineralized Water                                                                             →100                                        ______________________________________                                    

The acid activator was added to the sodium chlorite solution to producea sterilant system. The system was used to sterilize a number of testmedical instruments, for example endoscopes. After repeated treatment,no corrosion was observed. In a comparative test, a non-inhibited systemshowed that pitting was developing on metal parts.

I claim:
 1. A two-part sterilizing system comprising:(a) a first partcomprising sodium chlorite solution; and (b) a second part comprising anorganic acid and a corrosion inhibitor, said organic acid comprisescitric acid, sorbic acid, and boric acid, and said corrosion inhibitorcomprising a copper and brass corrosion inhibitor, a steel and aluminumcorrosion inhibitor, and a buffering agent; wherein said first part andsaid second part, when combined, provide a sterilizing compositionhaving a pH of about 5.5 or higher.
 2. A two-part sterilizing systemaccording to claim 1, wherein the copper and brass corrosion inhibitoris a triazole or benzotriazole present in a weight percent of 0.01 to2.0.
 3. The two-part sterilizing system according to claim 1, whereinthe steel and aluminum corrosion inhibitor is selected from the groupconsisting of phosphates, molybdates, and nitrates, and is present in aweight percent of from 0.01 to 5.0.
 4. The two-part sterilizing systemaccording to claim 1, further comprising a steel and ferric corrosioninhibitor comprising sodium nitrate.
 5. The two-part sterilizing systemaccording to claim 1, further comprising a sequestering agent.
 6. Thetwo-part sterilizing system according to claim 1, further comprising awetting agent, a defoamer, or a combination thereof.
 7. The two-partsterilizing system according to claim 1, wherein said buffering agentcomprises trisodium phosphate.
 8. A sterilizing compositioncomprising:(a) sodium chlorite solution; (b) an organic acid comprisingcitric acid, sorbic acid, and boric acid; (c) a buffering agentcomprising trisodium phosphate; (d) a corrosion inhibitor comprising acopper and brass corrosion inhibitor, and a steel and aluminum corrosioninhibitor.
 9. The composition according to claim 8, wherein saidcomposition has a pH of about 5.5 or higher.
 10. A method forsterilizing medical instruments, said method comprising:(a) preparing asterilizing composition by combining a first part comprising sodiumchlorite solution, and a second part comprising an organic acid, acorrosion inhibitor, and a buffering agent, wherein the organic acidcomprises citric acid, sorbic acid, and boric acid; (b) introducing amedical instrument into the sterilizing composition to effectsterilization of the medical instrument.
 11. The method for sterilizingmedical instruments according to claim 10, further comprising a stepof:(a) adjusting the pH of the sterilizing composition to about 5.5 orhigher.